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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)
 

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Immunogenicity of a Yersinia pestis Vaccine Antigen Monomerized by Circular Permutation.

Caf1, a chaperone-usher protein from Yersinia pestis, is a major protective antigen in the development of subunit vaccines against plague. However, recombinant Caf1 forms polymers of indeterminate size. We report the conversion of Caf1 from a polymer to a monomer by circular permutation of the gene. Biophysical evaluation confirmed that the engineered Caf1 was a folded monomer. We compared the immunogenicity of the engineered monomer with polymeric Caf1 in antigen presentation assays to CD4 T-cell hybridomas in vitro, as well as in the induction of antibody responses and protection against subcutaneous challenge with Y. pestis in vivo. In C57BL/6 mice, for which the major H-2(b)-restricted immunodominant CD4 T-cell epitopes were intact in the engineered monomer, immunogenicity and protective efficacy were preserved, although antibody titers were decreased 10-fold. Disruption of an H-2(d)-restricted immunodominant CD4 T-cell epitope during circular permutation resulted in a compromised T-cell response, a low postvaccination antibody titer, and a lack of protection of BALB/c mice. The use of circular permutation in vaccine design has not been reported previously.[1]

References

  1. Immunogenicity of a Yersinia pestis Vaccine Antigen Monomerized by Circular Permutation. Chalton, D.A., Musson, J.A., Flick-Smith, H., Walker, N., McGregor, A., Lamb, H.K., Williamson, E.D., Miller, J., Robinson, J.H., Lakey, J.H. Infect. Immun. (2006) [Pubmed]
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